Pharmacogenomics on the Treatment Response in Patients with Psoriasis: An Updated Review

Abstract

The efficacy and the safety of psoriasis medications have been proved in trials, but unideal responses and side effects are noted in clinical practice. Genetic predisposition is known to contribute to the pathogenesis of psoriasis. Hence, pharmacogenomics gives the hint of predictive treatment response individually. This review highlights the current pharmacogenetic and pharmacogenomic studies of medical therapy in psoriasis. HLA-Cw*06 status remains the most promising predictive treatment response in certain drugs. Numerous genetic variants (such as ABC transporter, DNMT3b, MTHFR, ANKLE1, IL-12B, IL-23R, MALT1, CDKAL1, IL17RA, IL1B, LY96, TLR2, etc.) are also found to be associated with treatment response for methotrexate, cyclosporin, acitretin, anti-TNF, anti-IL-12/23, anti-IL-17, anti-PDE4 agents, and topical therapy. Due to the high throughput sequencing technologies and the dramatic increase in sequencing cost, pharmacogenomic tests prior to treatment by whole exome sequencing or whole genome sequencing may be applied in clinical in the future. Further investigations are necessary to manifest potential genetic markers for psoriasis treatments.

Genome‑wide association study and polygenic risk scores predict psoriasis and its shared phenotypes in Taiwan

“…Psoriasis often causes significant psychological distress, which reduces the overall quality of life ( 9 ). Symptoms of psoriasis include distinct erythematous plaques on the skin, accompanied by silvery scales covering the affected areas, often accompanied by itching and pain ( 10 ). Clinical manifestations of psoriasis include subtypes such as plaque, guttate, nail, pustular, scalp and palmoplantar psoriasis ( 11 , 12 ).…”

“…A characteristic feature of psoriasis is the hyper-proliferation of keratinocytes, fibroblasts, and endothelial cells, triggering immune system activation, inflammatory response and new blood vessel formation (neovascularization or angiogenesis) ( 10 , 13 ). Genetic predispositions and environmental influences are significant factors that trigger these effects ( 3 , 11 ).…”

PDE4 Gene Family Variants Are Associated with Response to Apremilast Treatment in Psoriasis

“…The management of moderate-to-severe psoriasis involves various treatment approaches, i.e., first-line systemic drugs, small molecules, and biological agents [ 2 ]. Although these treatments are generally effective, they show considerable variation in response rates among patients [ 3 ]. It is estimated that 30–50% of the patients present an insufficient response to various treatments, which depends to a significant degree on the genetic background [ 4 ].…”

Gene Ontology Analysis Highlights Biological Processes Influencing Responsiveness to Biological Therapy in Psoriasis

“…Accumulating knowledge on the molecular pathways that underlie psoriasis has led to a better understanding of the disease’s development and is contributing to the development of promising potential treatment targets [ 18 ]. Numerous pharmacogenetic studies have researched the impact of genetic biomarkers on psoriasis disease response, especially to treatment with TNF-α inhibitors [ 19 , 20 ]. On the other hand, fewer pharmacogenetic studies have studied the treatment response to IL-12/23, IL-17 and IL-23 inhibitors [ 19 , 20 ].…”

“…Numerous pharmacogenetic studies have researched the impact of genetic biomarkers on psoriasis disease response, especially to treatment with TNF-α inhibitors [ 19 , 20 ]. On the other hand, fewer pharmacogenetic studies have studied the treatment response to IL-12/23, IL-17 and IL-23 inhibitors [ 19 , 20 ]. It is widely accepted that the response to treatment is heterogeneous, and it is hypothesized that 50–70% of response variation is due to the patients’ genetic background [ 21 ].…”